IDENTIFICATION OF NUCLEAR FACTOR THAT ACTIVATED THE XRE-MEDIATED GENE TRANSCRIPTION

芳烃受体（AHR）是一种配体激活的转录因子，可介导对2,3,7,8-四氯二苯并-对二恶英（TCDD）等环境污染物的生物反应。与野生型胚胎成纤维细胞相比，ahr缺失小鼠的胚胎成纤维细胞生长缓慢。在AHR缺失的EF中重新引入AHR可促进细胞生长，表明AHR参与细胞周期控制。利用腺病毒癌蛋白E1A检测AHR在细胞周期控制中的作用。EF来源于野生型和ahr缺失小鼠，用两种突变的E1A表达质粒转染，使p300/CBP或视网膜母细胞瘤蛋白（pRb）失活。尽管野生型EF的DNA合成均可由两种E1A突变体诱导，但无ahr的EF的DNA合成仅由与pRb结合的突变体诱导，而非与p300/CBP结合的突变体。这些数据表明，pRb和p300/CBP都是e1a诱导野生型EF DNA合成的靶点。然而，在AHR缺失的情况下，只有pRb是E1A诱导的DNA合成的目标，在没有AHR的情况下，p300/CBP不能被E1A灭活。免疫沉淀显示AHR直接与p300结合，这表明AHR通过与p300的相互作用参与细胞周期控制的有趣可能性。

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the biological responses to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Embryonic fibroblast (EF) isolated from AHR-null mice exhibited slow cell growth as compared with wild-type EF. Reintroduction of AHR into AHR-null EF increased cell growth, suggesting that AHR is involved in cell cycle control. The role of the AHR in cell cycle control was examined using the adenovirus oncoprotein E1A. EF, derived from wild-type and AHR-null mice, were transfected with two mutant E1A expression plasmids, that inactivate either p300/CBP or retinoblastoma protein (pRb). Although DNA synthesis of wild-type EF was induced by both E1A mutants, DNA synthesis in the AHR-null EF was induced only by the mutant that binds pRb but not by the mutant to p300/CBP. These data show that both pRb and p300/CBP were the target of E1A-induced DNA synthesis in wild-type EF. In AHR-null, however, only pRb was the target of E1A-induced DNA synthesis and p300/CBP cannot be inactivated by E1A in the absence of AHR. Immunoprecipitation revealed that AHR directly bound to p300 thus suggesting the intriguing possibility that AHR is involved in control of the cell cycle via interaction with p300.